This invention relates to sulfonyl benzimidazole derivatives. These compounds have selective cannabinoid(CB)2 receptor agonistic activity. The present invention also relates to a pharmaceutical composition, method of treatment and use, comprising the above derivatives for the treatment of disease conditions mediated by CB2 receptor activity; in particular CB2 receptor agonistic activity.
In general, CB2 receptor agonists are found to be useful for the treatment of a variety of diseases, including inflammatory pain, nociceptive pain, neuropathic pain, fibromyalgia, chronic low back pain, visceral pain, rheumatoid arthritis, Crohn's disease, ulcerative colitis, asthma, dermatitis, seasonal allergic rhinitis, gastroesophageal reflux disease (GERD), constipation, diarrhea, functional gastrointestinal disorder, irritable bowel syndrome, cutaneous T cell lymphoma, multiple sclerosis, osteoarthritis, psoriasis, systemic lupus erythematosus, diabetes, glaucoma, osteoporosis, glomerulonephritis, renal ischemia, nephritis, hepatitis, cerebral stroke, vasculitis, myocardial infarction, cerebral ischemia, reversible airway obstruction, adult respiratory disease syndrome, chronic obstructive pulmonary disease (COPD), cryptogenic fibrosing alveolitis and bronchitis (see J Pharmacol Exp Ther. 2004 February; 308(2):446-53; Proc Natl Acad Sci USA. 2003 Sep. 2; 100(18):10529-33; Br J. Pharmacol. 2004 August; 142(8):1247-54).
WO02/85866 discloses sulfonylamide compounds as CB2 agonists. Especially, compounds represented by the following formula is disclosed as Example 68:
Compound A
There is a need to provide new CB2 agonists that can be a good drug. In particular, preferred compounds should bind potently to the CB2 receptor whilst showing little affinity for other receptors and show functional activity as agonists. They should be well absorbed from the gastrointestinal tract, be metabolically stable and possess favorable pharmacokinetic properties. When targeted against receptors in the central nervous system they should cross the blood brain barrier freely. They should be non-toxic. Furthermore, the ideal drug candidate will exist in a physical form that is stable, non-hygroscopic and easily formulated.